Broadly conceived, my research objectives are to understand the relationship between the internal environment and behavior. Changes in the milieu interieur of an animal evoke certain behaviors (e.g., increases in blood osmotic pressure are followed by antidiuresis and drinking of water), behaviors which are regulatory in that they accomplish a return to a more or less homeostatic condition. The neural mechanisms which sense changes in the blood or other body fluids are of specific interest to me. Such internal sensing systems must be capable of transducing physicochemical fluctuations into some kind of cellular response, be it electrical, hormonal or both. The output of these internal "sense organs" must then be integrated into a directed behavior, appropriate to the prevailing circumstances. It is, however, the detectors of the imbalance which initiate the chain of events, and about which we known so little. The work proposed here will investigate the roles played in the osmodetection process by the cells in and around the paraventicular nucleus and the nucleus circularis of the hypothalamus. Consistent with our belief that no single technique or method gives unequivocal answers to biological questions, we will use a variety of approaches to characterize the system under study. These will include: light and electron microscopy, electrophysiological and anatomical analyses of osmotically and chemically induced changes both in vivo and hypothalamic slice preparations, immunohistochemistry, and transport methods.